I. To assess the safety and tolerability of this regimen in these patients. II. To observe
progression-free survival and response duration in patients treated with this regimen.

III. To observe the relationship between pretreatment lymphoma cell nuclear relA and
response in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior autologous
stem cell transplantation (yes vs no).

Patients receive oral vorinostat once daily on days 1-5 and 8-12. Patients also receive
bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 3 weeks in the absence of
disease progression, unacceptable toxicity, or requirement for palliative irradiation.
Patients who experience a complete or partial response after at least 1 year of study
therapy may discontinue treatment while remaining on study and then resume treatment at the
time of disease progression.

Archival or recent biopsy tissue specimens are obtained at baseline for laboratory
correlative studies. Samples are analyzed by IHC for expression of Rel A protein as a
predictive marker of response.

After completion of study therapy, patients are followed periodically.

- Measurable disease, defined as ≥ 1 lesion > 1.0 cm in diameter in both the long and
short axis, according to Revised Response Criteria for Malignant Lymphoma, as
measured by spiral CT scan or physical exam

- Must have histological material available for pathologic review and correlative
studies, including either of the following:

- Archival specimens from previous biopsies

- Specimens from repeat biopsy for histological confirmation in patients with
lymphoma that has undergone histological transformation in the past

- Fertile patients must use effective contraception prior to and during study treatment

- Able to tolerate loperamide or other anti-diarrheal medications

- Able to take oral medications

- No neuropathy ≥ grade 2

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to bortezomib or vorinostat

- No medical or other condition (e.g., uncontrolled infection or potentially
life-threatening changes on EKG) that would represent an inappropriate risk to the
patient or likely would compromise achievement of the primary study objective

- Able to understand and willing to sign a written informed consent document

- No concurrent treatment (e.g., marrow suppressive agents such as zidovudine) that
would represent an inappropriate risk to the patient or likely would compromise
achievement of the primary study objective

- Recovered from prior treatment

- No prior histone deacetylase inhibitor as cancer treatment

- No prior bortezomib

- Prior allogeneic stem cell transplantation allowed provided that all of the following
conditions are met:

- At least 6 months since allogeneic transplantation

- No graft-vs-host disease is present

- Not currently on immunosuppressive therapy

- More than 3 weeks since prior chemotherapy or large field radiotherapy

- No plan for other concurrent cancer treatment; If steroids for cancer control have
been used, patients must be off these agents for ≥ 1 week before starting treatment.
Exception: maintenance therapy for non-malignant disease with prednisone or steroid
equivalent dose < 10 mg/day is permitted

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